The blood contains large numbers of platelets, which are not entire cells but small detached cell fragments or "minicells" derived from the cortical cytoplasm of large cells called megakaryocytes. Platelets adhere specifically to the lining of damaged blood vessels, where they help repair breaches and aid in the process of blood clotting.
Unwanted platelet deposition occurs in a variety of disorders. Platelet deposition can lead to thrombosis, tissue ischemia and infarction. For example, intracoronary artery platelet deposition plays an important pathophysiologic role in unstable angina pectoris and reocclusion following percutaneous transluminal coronary artery angioplasty. Additionally, platelet deposition is involved in organ transplant rejection, pulmonary embolus, post vascular grafts and stents. Given this extensive list of disorders, effective detection of intravascular platelet deposition and diagnosis of the associated disorder has long been sought.
Previous techniques that have been employed to visualize platelet deposition have used the non-specific technique of "Indium tagging, Isaka et al., Thromb. Res., 56:739-749 (1989); Farlow, et al., Am. J. Cardiol., 64:363-368 (1989). This technique requires that the platelets first be removed from the patient, separated from the whole blood, labeled with .sup.111 Indium and then reinjected into the patient. The disadvantages of this method are (1) it requires several hours to perform, (2) the platelets may be partially activated during the process which may alter the biodistribution and carries a significant risk of intravascular platelet aggregation to the patient upon reinjection, and (3) the preparation of the platelets and in vitro labeling requires sterile technique and considerable experience. Because of these drawbacks the technique utilizing "Indium has not gained widespread use despite the significant clinical importance of such a detection method.
This invention provides the surprising and effective discovery that a thromboxane A.sub.2 receptor antagonist such as .sup.123 I-SAP, can be utilized to visualize disorders associated with intravascular platelet deposition. This method is easy, effective and has the following advantages over the current imaging technique utilizing .sup.111 Indium: (1) since the platelets do not require processing, sterile facilities and additional expertise in the handling of platelets is not required; (2) since processing is not required the method is safer; (3) since the compound is a thromboxane A.sub.2 receptor antagonist, there is not a risk of platelet aggregation; and (4) since only the presence of a radiopharmaceutical pharmacy and minimal imaging capabilities are required, the method can be utilized in most hospitals.